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1. 发明授权

US08088762B2 Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
标题翻译：硝化非甾体抗炎化合物，组合物和使用方法
公开(公告)号：US08088762B2
公开(公告)日：2012-01-03
申请号：US12636316
申请日：2009-12-11
申请人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/54 , A61K31/44 , A61K31/425 , C07D498/02 , C07D295/02 , C07D333/22
CPC分类号： C07D493/04 , C07C291/02 , C07C311/17 , C07C317/18 , C07C323/12 , C07C327/28 , C07D209/18 , C07D211/22 , C07D211/56
摘要： The invention describes novel nitrosated nonsteroidal anti-inflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
摘要翻译：本发明描述了新的亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，和任选的至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成一氧化氮，提高内源性内源水平的内源性松弛因子，或者是一氧化氮合成酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物合酶和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

2. 发明申请

US20110098253A1 Nitrosated Nonsteroidal Antiinflammatory Compounds, Compositions and Methods of Use 有权
标题翻译：亚硝化非甾体抗炎化合物，组合物和使用方法
公开(公告)号：US20110098253A1
公开(公告)日：2011-04-28
申请号：US12980077
申请日：2010-12-28
申请人： Richard Earl , Maiko Ezawa , Xinquin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： Richard Earl , Maiko Ezawa , Xinquin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/216 , A61K31/34 , A61K31/662 , A61K31/357 , A61K31/445 , A61K31/27 , A61K31/495 , A61K31/405 , A61K31/56 , A61K31/401 , A61P1/00 , A61P1/04 , A61P35/02 , A61P31/04 , A61P9/00 , A61P29/00 , A61P19/02 , A61P11/06 , A61P35/00 , A61P25/28
CPC分类号： C07D493/04 , C07C291/02 , C07C311/17 , C07C317/18 , C07C323/12 , C07C327/28 , C07D209/18 , C07D211/22 , C07D211/56
摘要： The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders comprising administration of novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent.
摘要翻译：本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 以及用于治疗和/或预防眼科疾病和/或病症，包括施用包含至少一种亚硝化NSAID的新组合物，和任选地至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的内源性放松因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种治疗剂的底物。

3. 发明授权

US07345037B2 Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders 失效
标题翻译：亚硝化和亚硝化化合物及其组合物及其用于治疗呼吸系统疾病的用途
公开(公告)号：US07345037B2
公开(公告)日：2008-03-18
申请号：US11604677
申请日：2006-11-28
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
IPC分类号： A61K31/40 , C07D451/00
CPC分类号： C07D451/06 , C07C313/36 , C07D311/22 , C07D451/10 , C07D471/04 , C07J5/00 , C07J7/00 , C07J31/00 , C07J71/00 , C07J71/0031
摘要： Disclosed are (i) compounds of a steroid, a β-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, β-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO.) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
摘要翻译：公开的是（i）直接或间接连接到NO或NO 2基团或基团上的基团的类固醇，β-激动剂，抗胆碱能药，肥大细胞稳定剂和磷酸二酯酶（PDE）抑制剂的化合物其在体内刺激NO或EDRF的内源性产生; （ii）类固醇，β-激动剂，抗胆碱能药物，肥大细胞稳定剂和PDE抑制剂的组合物，其可任选地被至少一个NO或NO 2个部分取代，或刺激内源性产生NO 或EDRF，以及作为带电物质，即亚硝酸盐（硝酸）或硝酰基（NO +）的一氧化氮，或NOX + 作为中性物种，一氧化氮（NO））或者在体内刺激NO或EDRF的内源性产生; 和（iii）用于预防和/或治疗呼吸系统疾病。

4. 发明授权

US07282519B2 Nitrosated and nitrosylated diuretic compounds, compositions and methods of use 失效
标题翻译：硝化和亚硝化利尿剂，组合物和使用方法
公开(公告)号：US07282519B2
公开(公告)日：2007-10-16
申请号：US10921936
申请日：2004-08-20
申请人： David S. Garvey , L. Gordon Letts , Manuel Worcel , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson
发明人： David S. Garvey , L. Gordon Letts , Manuel Worcel , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson
IPC分类号： A61K31/34 , A61K31/44 , A61K31/497 , C07D307/52
CPC分类号： C07D403/10 , C07C205/40 , C07D233/68 , C07D235/18 , C07D257/04 , C07D307/52 , C07D401/12 , C07D401/14 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/10 , C07D471/04 , C07D487/04 , C07D495/04 , C07D498/04
摘要： The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (l) treating nephropathy.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的利尿剂或其药学上可接受的盐，以及包含至少一种亚硝化和/或亚硝基化的利尿剂化合物和任选的至少一种一氧化氮供体和/或至少一种治疗剂。本发明还提供了包含至少一种本发明的利尿剂化合物，其任选被亚硝化和/或亚硝基化的新组合物和试剂盒，以及任选的至少一种一氧化氮供体化合物和/或至少一种治疗剂。本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; 和（l）治疗肾病。

5. 发明授权

US07129251B2 Nitrosated and nitrosylated H2 receptor antagonist compounds, compositions and methods of use 失效
标题翻译：亚硝化和亚硝基化H 2受体拮抗剂化合物，组合物和使用方法
公开(公告)号：US07129251B2
公开(公告)日：2006-10-31
申请号：US11180790
申请日：2005-07-14
申请人： David S. Garvey , L. Gordon Letts , Chia-En Lin , Tiansheng Wang
发明人： David S. Garvey , L. Gordon Letts , Chia-En Lin , Tiansheng Wang
IPC分类号： C07D295/14 , A61K31/445 , A61P1/04
CPC分类号： C07D233/54 , C07D233/64 , C07D277/48 , C07D295/092 , C07D295/096
摘要： The invention describes novel nitrosated and/or nitrosylated H2 receptor antagonist compounds, and novel compositions comprising at least one H2 receptor antagonist compound that is optionally substituted with at least one NO and/or NO2 group, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase and/or at least one nonsteroidal antiinflammatory drug, antacid, bismuth-containing reagent or anti-viral agent. The invention also describes methods for treating and/or preventing gastrointestinal disorders; improving gastroprotective properties of H2 receptor antagonists; decreasing the recurrence of ulcers; facilitating ulcer healing; preventing and/or treating inflammations and microbial infections, ophthalmic diseases and disorders, multiple sclerosis, and viral infections; and decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的H 2 O 2受体拮抗剂化合物，以及包含至少一种H 2受体拮抗剂化合物的新组合物，其任选被至少一个NO 和/或NO 2个基团，以及任选地，至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成，提高内源性内皮水平的内源性松弛因子，或者是一氧化氮合酶的底物和/或至少一种非甾体抗炎药，抗酸剂，含铋试剂或抗病毒剂。本发明还描述了治疗和/或预防胃肠道疾病的方法; 改善H 2受体拮抗剂的胃保护性质; 减少溃疡复发; 促进溃疡愈合; 预防和/或治疗炎症和微生物感染，眼科疾病和病症，多发性硬化和病毒感染; 并减少或减少与使用非甾体抗炎化合物相关的胃肠道毒性。

6. 发明授权

US5824669A Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders 失效
标题翻译：亚硝化和亚硝化化合物及其组合物及其用于治疗呼吸系统疾病的用途
公开(公告)号：US5824669A
公开(公告)日：1998-10-20
申请号：US620882
申请日：1996-03-22
申请人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
发明人： David S. Garvey , L. Gordon Letts , H. Burt Renfroe , Stewart K. Richardson
IPC分类号： A61K31/00 , A61K31/56 , A61K31/58 , A61K45/00 , A61P11/00 , C07C313/36 , C07D311/22 , C07D451/06 , C07D451/10 , C07D471/04 , C07J5/00 , C07J7/00 , C07J31/00 , C07J71/00
CPC分类号： C07D451/06 , C07C313/36 , C07D311/22 , C07D451/10 , C07D471/04 , C07J31/00 , C07J5/00 , C07J7/00 , C07J71/00 , C07J71/0031
摘要： Disclosed are (i) compounds of a steroid, a .beta.-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO.sub.2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, .beta.-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO.sub.2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO.sup.+) or nitroxyl (NO.sup.-), or as the neutral species, nitric oxide (NO.circle-solid.) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
摘要翻译：公开的是（i）直接或间接连接到NO或NO 2基团或刺激NO或EDRF的内源性产生的组的类固醇，β-拮抗剂，抗胆碱能药，肥大细胞稳定剂和磷酸二酯酶（PDE）抑制剂的化合物体内; （ii）类固醇，β-激动剂，抗胆碱能药物，肥大细胞稳定剂和PDE抑制剂的组合物，其可任选地被至少一个NO或NO 2部分或刺激体内NO或EDRF内源性产生的基团取代;以及化合物捐赠，转移或释放一氧化氮作为带电物种，即亚硝酸盐（NO +）或硝酰基（NO-），或作为中性物质，一氧化氮（NO + 574）或刺激体内NO或EDRF的内源性产生 ; 和（iii）用于预防和/或治疗呼吸系统疾病。

7. 发明授权

US07772278B2 Nitrosated and nitrosylated prostaglandins, compositions and methods of use 失效
标题翻译：亚硝化和亚硝酰化前列腺素，组合物和使用方法
公开(公告)号：US07772278B2
公开(公告)日：2010-08-10
申请号：US12237117
申请日：2008-09-24
申请人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
发明人： David S. Garvey , Ricky D. Gaston , L. Gordon Letts , Inigo Saenz de Tejada , Sang William Tam , Manuel Worcel
IPC分类号： A61K31/557 , C07C405/00
CPC分类号： A61K31/5575
摘要： The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
摘要翻译：本发明描述了新的亚硝化和/或亚硝基化的前列腺素，以及包含至少一种亚硝化和/或亚硝基化的前列腺素的新组合物，以及任选的至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的放松因子，刺激一氧化氮的内源性合成或是一氧化氮合酶的底物和/或至少一种血管活性剂。本发明还提供了包含至少一种前列腺素和至少一种S-亚硝基硫醇化合物和任选的至少一种血管活性剂的新型组合物。前列腺素优选为前列腺素E1化合物，更优选前列地尔，S-亚硝基硫醇化合物优选为S-亚硝基谷胱甘肽。本发明还提供用于治疗或预防男性和女性的性功能障碍的方法，用于增强男性和女性的性反应，以及用于治疗或预防脑血管疾病，心血管疾病，良性前列腺增生（BPH），青光眼，消化性溃疡或诱导堕胎

8. 发明授权

US07754772B2 Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use 有权
标题翻译：硝化非甾体抗炎化合物，组合物和使用方法
公开(公告)号：US07754772B2
公开(公告)日：2010-07-13
申请号：US11134358
申请日：2005-05-23
申请人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： Richard A. Earl , Maiko Ezawa , Xinqin Fang , David S. Garvey , Ricky D. Gaston , Subhash P. Khanapure , L. Gordon Letts , Chia-En Lin , Ramani R. Ranatunge , Stewart K. Richardson , Joseph D. Schroeder , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： A61K31/135 , C07C203/04
CPC分类号： C07D493/04 , C07C291/02 , C07C311/17 , C07C317/18 , C07C323/12 , C07C327/28 , C07D209/18 , C07D211/22 , C07D211/56
摘要： The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
摘要翻译：本发明描述了新型亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，以及任选地至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成升高内源性内源性松弛因子水平，或是一氧化氮合酶的底物和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物合酶和/或至少一种治疗剂。本发明还提供了包含至少一种亚硝化NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

9. 发明授权

US07595313B2 Nitric oxide donating diuretic compounds, compositions and methods of use 失效
标题翻译：一氧化氮供应利尿剂，组合物和使用方法
公开(公告)号：US07595313B2
公开(公告)日：2009-09-29
申请号：US12136531
申请日：2008-06-10
申请人： David S. Garvey , L. Gordon Letts , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Ricky D. Gaston , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson , Shiow-Jyi Wey
发明人： David S. Garvey , L. Gordon Letts , Richard A. Earl , Maiko Ezawa , Xinqin Fang , Ricky D. Gaston , Subhash P. Khanapure , Chia-En Lin , Ramani R. Ranatunge , Cheri A. Stevenson , Shiow-Jyi Wey
IPC分类号： C07D285/24 , C07D417/04 , C07D513/10 , A61K31/549
CPC分类号： C07D285/30 , C07D285/28 , C07D285/32 , C07D417/04 , C07D417/06 , C07D513/10
摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.
摘要翻译：本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

10. 发明授权

US07589124B2 Nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use 失效
标题翻译：亚硝化和/或亚硝基化的环氧合酶-2选择性抑制剂，组合物和使用方法
公开(公告)号：US07589124B2
公开(公告)日：2009-09-15
申请号：US11730886
申请日：2007-04-04
申请人： L. Gordon Letts , David S. Garvey
发明人： L. Gordon Letts , David S. Garvey
IPC分类号： A61K31/34 , C07C229/42
CPC分类号： C07D295/185 , A61K45/06 , C07C229/42 , C07C317/18 , C07C323/12 , C07D493/04
摘要： The invention provides novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions and kits comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.
摘要翻译：本发明提供新的亚硝化和/或亚硝基化的环氧合酶2（COX-2）选择性抑制剂和包含至少一种亚硝化和/或亚硝基化的环氧合酶2（COX-2）选择性抑制剂的新组合物和试剂盒，以及任选的至少一种化合物捐赠，转移或释放一氧化氮，刺激一氧化氮的内源性合成，提高内源性内皮衍生的松弛因子水平，或者是一氧化氮合酶的底物和/或任选的至少一种治疗剂。本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗和/或改善COX-2选择性抑制剂的胃肠性质; 促进伤口愈合; 用于治疗和/或预防肾和/或呼吸毒性; 用于治疗和/或预防由环氧合酶-2水平升高引起的其他疾病; 并用于改善COX-2选择性抑制剂的心血管外形。

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